My research involves the characterization of the role of IMMP2L, a protease of the mitochondrial intermembrane space, in mitochondrial biogenesis in mammalian systems. Dysfunction of IMMP2L has been linked to Tourette's syndrome. Since the molecular basis of Tourette's syndrome might be caused by inefficient processing of mitochondrial intermembrane space proteins and subsequent accumulation of unprocessed polypeptides, I propose to develop a mouse knock-out model of IMMP2L. The disruption of IMMP2L most likely leads to a decreased gene dosage, so I expect that a heterozygous knock-out should show symptoms. With the model, we will study the accumulation of intermembrane space (IMS) proteins that are processed by IMMP2L. Additionally, I will create IMMP2L knock-out lines from embryonic stem cells and perform in vitro import assays to determine if SMAC/Diablo, AIF, and other IMS proteins are processed properly. Finally, using S. cerevisiae as a model system, I will undertake complementation studies to determine if IMMP2L will function in place of the yeast homolog, IMP2. Results of this project may lead to developing effective treatments to combat neural diseases caused by defects in mitochondria such as Tourette's Syndrome.